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Causality between telomere length and breast diseases: a two-sample bidirectional Mendelian randomization study.

Simin Luo1, Jie Chai1, Yangyang Cai1

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Longer telomere length increases the risk of breast cancer, benign breast neoplasm, and breast inflammation. However, breast diseases do not appear to causally influence telomere length, warranting further investigation.

Keywords:
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Area of Science:

  • Genetics and Epidemiology
  • Oncology

Background:

  • The link between telomere length and breast diseases, including breast cancer, is not well-established, with existing evidence being contradictory.
  • Previous studies have yielded conflicting results regarding the association between telomere length and various breast conditions.

Purpose of the Study:

  • To investigate the bidirectional causal relationship between telomere length and breast diseases using a robust genetic approach.
  • To clarify the etiological role of telomere length in the development of breast cancer, benign breast neoplasms, and breast inflammation.

Main Methods:

  • Utilized genome-wide association study (GWAS) data for telomere length, breast cancer, benign neoplasm of breast, and breast inflammation.
  • Employed Mendelian randomization (MR) analysis to assess the causal effects in both directions: telomere length as exposure and breast diseases as outcome, and vice versa.

Main Results:

  • Increased telomere length was significantly associated with a higher risk of breast cancer (OR=1.130), benign neoplasm of breast (OR=1.002), and breast inflammation (OR=1.487).
  • The reverse Mendelian randomization analysis indicated no significant causal effect of breast cancer or benign neoplasm of breast on telomere length.
  • The causal relationship between breast inflammation and telomere length in the reverse direction could not be definitively determined.

Conclusions:

  • Telomere length acts as a significant risk factor for developing breast diseases, with longer telomeres elevating the risk.
  • The study did not find evidence for a causal role of breast cancer or benign breast neoplasms in influencing telomere length.
  • Further research is recommended to validate these findings, particularly in diverse ethnic populations.